Immune environment in serrated lesions of the colon: intraepithelial lymphocyte density, PD-1, and PD-L1 expression correlate with serrated neoplasia pathway progression

Human Pathology
Gabriel Acosta-GonzalezMurray B Resnick

Abstract

The serrated neoplasia pathway accounts for approximately 20% of colorectal carcinomas (CRCs). Sessile serrated adenomas (SSAs), the main precursor lesion of the serrated pathway, are molecularly driven by MLH1 promoter methylation and microsatellite instability (MSI) in their progression to CRC. MSI-high (MSI-H) lesions are highly immunogenic and associated with a high density of tumor-infiltrating lymphocytes. Our study's aim was to determine how the kinetics of this immune environment relates to SSAs in their progression through low-grade (SSA-LD) to high-grade dysplasia (SSA-HD) and CRC. We analyzed 74 cases (16 CRCs, 14 SSAs-HD, and 44 SSAs-LD). Cases of hyperplastic polyp and SSA without dysplasia were analyzed for comparison. MSI status, intraepithelial lymphocyte (IEL) density, and immune checkpoint expression were assessed by immunohistochemistry for mismatch repair proteins, CD3, and PD-1/PD-L1, respectively. Average IEL density was 12, 18.6, 21.6, and 31 for SSA, SSA-LD, SSA-HD, and CRC, respectively, as opposed to 8.1 in normal colon (P < .0001). Average PD-1/PD-L1 lymphocytic expression was 1.1/1.0, 1.2/2.9, 4.8/6.9, and 12.4/15.2 in SSA, SSA-LD, SSA-HD, and CRC, respectively, compared with 0.5/0 in normal crypts (...Continue Reading

References

Feb 13, 2001·The American Journal of Pathology·J AlexanderS R Hamilton
Oct 3, 2008·The American Journal of Surgical Pathology·Joel K GreensonStephen B Gruber
Jun 9, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·David TougeronJean-Baptiste Latouche
Sep 28, 2010·Human Pathology·Dale C Snover
Jan 26, 2011·The American Journal of Surgical Pathology·Kohei FujitaYoshinao Oda
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Jun 20, 2012·The American Journal of Gastroenterology·Douglas K RexJames Church
Mar 12, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Kenneth FriedmanMurray B Resnick
May 21, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Matthew W RosenbaumMari Mino-Kenudson
Oct 28, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Lik Hang LeeJinru Shia
Jul 29, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Cheng LiuChristophe Rosty
Dec 23, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Odise CenajRobert D Odze

❮ Previous
Next ❯

Citations

Nov 15, 2019·Virchows Archiv : an International Journal of Pathology·Matteo FassanFotios Loupakis
Dec 4, 2020·World Journal of Gastroenterology : WJG·Milena PeruhovaTsvetelina Veselinova Velikova
Aug 4, 2021·Cancer Prevention Research·Kristin WallaceAlexander V Alekseyenko

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.